Leukemia Pediatric Patient

Review ArticleOral and Dental Considerations in Pediatric Leukemic Patient

Chiyadu Padmini1,2 and K. Yellamma Bai2,3

1 Department of Pedodontics and Preventive Dentistry, Malla Reddy Institute of Dental Sciences, Hyderabad, Andhra Pradesh, India2NTR University of Health Sciences, Vijayawada, Andhra Pradesh, India3 Department of Pedodontics and Preventive Dentistry, Mally Reddy Women’s Dental College, Hyderabad, Andhra Pradesh, India

Correspondence should be addressed to Chiyadu Padmini; [email protected]

Received 7 December 2013; Accepted 17 January 2014; Published 4 March 2014

Academic Editors: C. Gruellich and E. M. Rego

Copyright © 2014 C. Padmini and K. Y. Bai. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Throughout the world, there have been drastic decline in mortality rate in pediatric leukemic population due to early diagnosis andimprovements in oncology treatment. The pediatric dentist plays an important role in the prevention, stabilization, and treatmentof oral and dental problems that can compromise the child’s health and quality of life during, and follow up of the cancer treatment.This manuscript discusses recommendations and promotes dental care of the pediatric leukemic patients.

1. Introduction

Leukemia constitutes approximately 30% of all childhoodcancers and acute lymphoblastic leukaemia (ALL) is themostcommon type of malignancy encountered in children [1, 2].ALL accounts for about 75% of childhood leukemias withits peak incidence at 4 years of age [3]. Acute lymphoblasticleukemia (ALL) is a malignant disorder resulting from theclonal proliferation of lymphoid precursors with arrestedmaturation [4]. The disease can originate in lymphoid cellsof different lineages, thus giving rise to B-cell or T-cellleukemias or sometimes to mixed lineage leukemia. Acutelymphoblastic leukemia was one of the first malignanciesto respond to chemotherapy [5]. Among various leukemiacategories, it was the first leukemia that could be cured in amajority of children [6]. Since then, much progress has beenmade, not only in terms of treatment but also in preventionof oral problems due to cancer treatment in children.

The most common signs and symptoms of ALL areanorexia, irritability, lethargy, anemia, bleeding, petechiae,fever, lymphadenopathy, hepatosplenomegaly, and bone painand arthralgias caused either by leukemic infiltration of theperichondral bone or joint or by leukemic expansion ofthe bone marrow cavity leading to disability in walking inchildren [3]. The most common head, neck, and intraoral

manifestations of ALL at the time of diagnosis are lym-phadenopathy, sore throat, laryngeal pain, gingival bleeding,and oral ulceration [7]; see Table 1.

2. Methods

The current paper revision included a new systematic liter-ature search of the PubMed electronic data base using thefollowing parameters: terms: “pediatric cancer,” “pediatriconcology,” “hematopoietic cell transplantation,” “bone mar-row transplantation,” “mucositis,” “stomatitis,” “chemother-apy,” “radiotherapy,” “acute effects,” “long-term effects,” “den-tal care,” “oral health,” and “pediatric dentistry.”

3. The Oncology Treatment of AcuteLymphoblastic Leukemia Is Divided intoFour Phases [8]

(1) Remission Induction. It generally lasts for 28 days andconsists of 3 or 4 drugs (examples are vincristine, prednisone,and L-asparaginase), with a 95% success rate. Achievement ofremission is a known prerequisite for prolonged survival.

(2) CNS Preventive Therapy/Prophylaxis. CNS can act as asanctuary site for leukemic infiltrates because systemically

Hindawi Publishing CorporationISRN HematologyVolume 2014, Article ID 895721, 11 pageshttp://dx.doi.org/10.1155/2014/895721

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Table 1: World Health Organization (WHO) recommendations forgrading of acute and subacute toxic effects [10].

Grade Symptoms0 None1 Soreness/erythema2 Erythema/ulcers/can eat solids3 Ulcers/require liquid food4 Alimentation is not possible

administered chemotherapeutic drugs are not able to crossthe blood-brain barrier. Cranial irradiation and/or weeklyintrathecal injection of a chemotherapeutic agent, usuallymethotrexate, are used. This presymptomatic treatment canbe done in each phase as well.

(3) Consolidation or Intensification. It is designed tominimizethe development of drug cross-resistance through intensifiedtreatment, in an attempt to kill any remaining leukemic cells.

(4) Maintenance. It is aimed at suppressing leukemic growththrough continuous administration of methotrexate and 6-mercaptopurine. The optimal length of this phase has notbeen established yet but usually lasts from 2.5 to 3 years.

The patient’s blood counts normally start falling five toseven days after the beginning of each cycle of chemotherapyand/or radiotherapy staying low for approximately 14 to 21days before rising again to normal levels for a few daysuntil the next cycle begins [8]. A multidisciplinary approachinvolving oncologists, nurses, dieticians, pediatric dentists,and other related health professionals is essential in caring forthe child before, during, and after any cancer therapy [9].

Ideally, all dental care should be completed before cancertherapy is initiated, and if it is not feasible, priority treatmentsshould be eradicating acute infectious sources like extractionof grossly decayed teeth, periodontal diseases, root canaltherapy for permanent teeth, and replacement of faultyrestorations to avoid oral tissue irritation [15]. The oralmucosa is highly susceptible to the effects of chemotherapyand radiotherapy due high mitotic activity and is the mostfrequently documented source of sepsis in the immunosup-pressed pediatric leukemic patients. For these reasons, earlyand definitive dental intervention, including comprehensiveoral hygienemeasures, reduces the risk for oral and associatedsystemic complications [15].

The dental treatment for leukemic children can bebroadly divided into 3 phases [8]:

phase 1: dental and oral care before the initiation ofcancer therapy,phase 2: dental and oral care during immunosuppres-sion periods,phase 3: dental and oral care after the cancer therapyis completed.

3.1. Phase 1: Dental and Oral Care before the Initiation ofCancer Therapy. The objectives of a dental/oral examinationbefore cancer therapy starts are stated below [16]:

(1) to identify and stabilize or eliminate existing andpotential sources of infection and local irritants inthe oral cavity without needlessly delaying the cancertreatment or inducing complications. Any existinglesions that might normally lie dormant can flare upand become life threatening once the child is immunesuppressed;

(2) to educate the patient and parents about the impor-tance of optimal oral care in order to minimize oralproblems and discomfort before, during, and aftertreatment and about the possible acute and long-term effects of the therapy in the oral cavity and thecraniofacial complex; see Table 6.

Initial evaluation of oral and dental examination includes

(1) reviewing the child medical history,(2) reviewing current hematological status,(3) reviewing the proposed chemotherapy/radiation pro-

tocol,(4) completing a thorough head, neck, and dental exam-

ination including panoramic and bitewing radio-graphs.

Medical history review includes disease/condition (type,stage, and prognosis), treatment protocol (conditioning regi-men, surgery, chemotherapy, radiation, and transplant),med-ications (including bisphosphonates), allergies, surgeries,secondarymedical diagnoses, hematological status (completeblood count (CBC)), coagulation status, immune suppressionstatus, and presence of an indwelling venous access line.Most of the leukemic patients have a central line, whichis an indwelling catheter inserted into the right atrium ofthe heart, which is useful for obtaining blood samples andadministering chemotherapeutic agents.TheAmericanHeartAssociation (AHA) recommends that antibiotic prophylaxisfor non valvular heart devices is indicated only at the time ofplacement of these devices in order to prevent surgical siteinfections [17].

3.1.1. Hematological Considerations

(1) Absolute Neutrophil Count (ANC). ANC > 1,000/mm3:there is no need for antibiotic prophylaxis [15]. However,few authors suggest that antibiotic coverage dose (as perAmerican Heart Association recommendations [18]) may beprescribed when the ANC is between 1,000 and 2,000/mm3[19]. If infection is present or unclear, more aggressiveantibiotic therapy may be indicated and should be discussedwith the medical team.

ANC < 1,000/mm3: elective dental care should bedeferred until the ANC rises. In case of dental emergency,discussion should be done with medical team regardingantibiotic coverage beyond endocarditis prophylaxis beforeproceeding for dental treatment.

(2) Platelet Count [15]. Platelet count > 75,000/mm3: thereis no need of additional support but thedentist should

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be prepared to treat prolonged bleeding by using sutures,hemostatic agents, pressure packs, gelatin foams, and so forth.

Platelet count is 40,000 to 75,000/mm3: platelet transfu-sions may be considered pre- and 24 hours postoperatively.Localized procedures to manage prolonged bleeding mayinclude sutures, hemostatic agents, pressure packs, and/orgelatin foams.

Platelet count < 40,000/mm3: elective dental care shouldbe deferred. In dental emergency cases, discussion should bedone with patient’s physician to discuss supportive measures(e.g., platelet transfusions, bleeding control, and hospitaladmission) before proceeding.

Meticulous oral care is important to reduce the incidenceand severity of oral sequelae of the treatment protocol.Parents and child should be educated about the importanceof good oral hygiene practices throughout the entire oncologytreatment, regardless of the child’s hematological status [20].

A regular soft toothbrush or an electric brush used atleast twice daily is the most efficient means to reduce therisk of significant bleeding and infection in the gingiva[21]. Periodontal problems should be eliminated primarilybecause chemotherapeutic treatment could stimulate myelo-suppression, and during myelosuppression period chronicperiodontal situations could show an acute attack [22].Leukemic children who present poor oral hygiene or peri-odontal disease are prescribed chlorhexidine rinses [19].Mouth rinses containing alcohol should be avoided becausethey can dry the mucosa and aggravate mucositis. Sodiumbicarbonate or saline mouthwash 3 or 4 times a day couldalso be recommended for these patients. Sodium bicarbonate(5%) could dilute the mucous secretion, moisten the oralmucosa, increase the oral pH, and inhibit the Candidaalbicans colonization [23].

The leukemic child may be at high risk for dental cariesfrom a dietary standpoint for a number of reasons as patientsare prescribed daily nutritional supplements rich in carbohy-drate to maintain or gain weight and oral pediatric medica-tions contain high amounts of sucrose (e.g., nystatin) whichmakes them prone for dental caries. So fluoride supplementsand neutral fluoride rinses or gels are indicated for thosepatients who are at risk for caries. Use of 0.12% chlorhexidinemouthwash twice daily has been found to effectively suppressthe major pathogens present in the oral cavity [24]. Teethwith poor prognosis (e.g., impacted teeth, root tips, partiallyerupted thirdmolars, teeth with periodontal pockets > 5mm,teeth with acute infections, and nonrestorable teeth) shouldbe removed ideally 3 weeks before cancer therapy starts toallow adequate healing and special attention to be given toextraction of permanent teeth in patients who will receive orhave already received radiation to the face as it poses a risk ofosteoradionecrosis [25, 26]. All surgical procedures must beas atraumatic as possible, with no sharp bony edges remainingand satisfactory closure of the wounds [27]. A platelet countof 50,000/mm3 is advisable for minor surgeries like simpleextractions, whereas a minimum level of 100,000/mm3 isdesirable for major surgeries like removal of impacted teeth[28].The local hemostatic measures must be considered such

as pressure packs, sutures, use of a gelatin sponge, and topicalthrombin or microfibrillar collagen.

Fixed orthodontic appliances can harbor food debris,compromise oral hygiene, and act as mechanical irritants,increasing the risk for secondary infection. Removable appli-ances and retainers must be advised when tolerated by thepatient who shows good oral care. Dahllof et al. described thefollowing strategies to provide orthodontic care for pediatricleukemic patients [29]:

(1) usage of appliances that minimize the risk of rootresorption,

(2) use of lighter forces,(3) terminating treatment earlier than normal,(4) choosing the simplest method for the treatment

needs,(5) not treating the lower jaw.

3.2. Phase 2: Dental and Oral Care duringImmunosuppression Periods

3.2.1. Objectives [16]. The objectives of a dental/oral careduring cancer therapy are stated below:

(1) to maintain optimal oral health during cancer ther-apy,

(2) to manage any oral side effects that may develop as aconsequence of the cancer therapy,

(3) to reinforce the patient and parents’ education regard-ing the importance of optimal oral care in orderto minimize oral problems/discomfort during treat-ment.

Acute manifestations that develop during immune sup-pression are mucositis, gingival bleeding, xerostomia, sec-ondary candidiasis, and herpes simplex and bacterial infec-tions. Mucosal ulceration is the most frequent oral problemencountered and is associatedwith lowneutrophil counts andthe aim of oral management is to relieve symptoms and toprevent and treat any secondary infection [30].

3.2.2. Clinical Significance ofMucositis. Oralmucositis can bevery painful condition and can significantly affect nutritionalintake, mouth care, and quality of life of leukemic child [31].Oral mucositis typically arises within two weeks after initia-tion of chemotherapy and agents such as antimetabolites andalkylating agents cause a higher incidence and severity of oralmucositis in children [32]. Oral mucositis initially presents aserythema of the oral mucosa that often progresses to erosionand ulceration. A white fibrinous pseudomembrane typicallycovers the ulcerations and lesions heal within approximately2–4 weeks after the last dose of stomatotoxic chemotherapyor radiation therapy [33].

Several factors affect the clinical course of mucositis.In chemotherapy-induced oral mucositis, lesions are usuallylimited to nonkeratinized surfaces (i.e., lateral and ventraltongue, buccal mucosa, and soft palate) [34]. In radiation-induced oral mucositis, lesions are limited to the tissues in

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Table 2: “Common terminology criteria for adverse events,” version4.0. advocated by National Cancer Institute (NCI) [11].

Grade Symptoms

0 Asymptomatic/mild symptoms; intervention notindicated.

1 Moderate pain; no interference with oral intake;modified diet indicated.

2 Severe pain; interference with oral intake.

3 Life threatening consequences; urgentintervention required.

4 Death.

the field of radiation with nonkeratinized tissues affectedmore often. The clinical severity is directly proportional tothe dose of radiation administered [35]. A study conductedby Elting et al., demonstrated that patients with oralmucositisare significantly more likely to have severe pain and a weightloss of ≥ 5% compared to controls [36].

In a study conducted by Trotti et al., they proved thatapproximately 16% of patients receiving radiation therapy forhead and neck cancer were hospitalized due to mucositisand among them 11% of the patients had unplanned breaksin radiation therapy due to severe mucositis [37]. Thus, oralmucositis is amajor dose limiting toxicity of radiation therapythat in turn compromises treatment plan and its outcome.

Maintenance of good oral hygiene reduces the severity ofmucositis. A study done by Da Fonseca proved that thosepatients who do intensive oral care have a reduced riskof developing moderate/severe mucositis and its associatedcomplications like infections and septicemia [38].

3.2.3. Assessment Scales for Oral Mucositis [39]. Mucositisseverity should be graded using a validated scale, such as theWHOscale, prior to initiating supportive therapy, to establisha baseline and to assess the treatment outcome.

The WHO scale describes the degree of soreness, ery-thema, and ability of the child to have normal diet. Patientswith grade I and grade II mucositis should brush theirteeth as described earlier with a soft toothbrush and fluoridetoothpaste and rinse with a salt and bicarbonate solution.

With grade III mucositis, children should be advised toclean the oral cavity 4 times a day as described earlier or withgauze dipped in a salt and bicarbonate solution. The salt andbicarbonate solutions should be used every 4 to 6 hours ifpossible. Grade IV mucositis requires the patient to cleansethe oral cavity 4 times a day with either a soft toothbrush orgauze and to use a salt and bicarbonate solution every 4 hours.

The Cancer Institute scale describes the severity of pain,change in oral intake, and death related to mucositis.

Oral Assessment Guide reviews the extent of mucositis ingreater depth in the pediatric population compared to WHOand NCI scales; see Tables 1, 2, and 3.

3.2.4. Oral Care Protocols [39]. A standard first step toprevent mucosal injury is the implementation of good oralhygiene and the use of a standardized oral care protocol for

all children undergoing chemotherapy. Various authors inliterature have studied a number of oral care protocols.

Cheng et al. conducted a study on the effectiveness ofan oral care protocol for the prevention of chemotherapy-induced oral mucositis in children. The protocol was evalu-ated over an 8-month period in 42 pediatric cancer patientswho ranged in age from 6 to 17 years.

The results obtained from this study were significant anddemonstrated a 38% reduction in the incidence and severityof ulcerative mucositis along with decrease in pain in theexperimental group who were instructed to follow propertechnique of toothbrushing, 0.2% chlorhexidinemouth rinse,whichwas used twice a day, and a 0.9% saline rinse, whichwasused in the morning, after each meal and before going to bed[40].

Costa et al., evaluated 14 children, whose ages rangedfrom 2 to 10 years. Oral health protocol began at least 1 daybefore initiating the chemotherapy and ended 10 days afterthe end of this period. The average length of treatment was8 weeks. The treatment group consisted of 7 patients whoreceived a mouth rinse with a nonalcoholic solution of 0.12%chlorhexidine and oral hygiene care, including twice-dailytoothbrushing.The control group followed the same protocolfor brushing their teeth but was given a placebo mouth rinse.The results were considered statistically significant. Only 1child from the treatment group, compared to 5 children inthe control group, developed oral mucositis. The oral lesionswere less severe and of a shorter duration in the children whoreceived chlorhexidine mouth rinses [41].

3.2.5. Clinical Management of Oral Mucositis [33]. A varietyof nonpharmacological and pharmacological agents havebeen used in practice for the prevention and management oforal mucositis in children. There is no gold standard at thistime, as there is a lack of evidence-based recommendations.So research should be focused to bring a gold standardtreatment protocol for oral care in children. MultinationalAssociation for Supportive Care in Cancer and the Inter-national Society of Oral Oncology (MASCC/ISOO) havedeveloped clinical practice guidelines for the management ofmucositis.

Management of oral mucositis in children is divided intothe following sections:

(1) pain control,(2) nutritional support,(3) oral decontamination,(4) palliation of dry mouth,(5) management of oral bleeding and therapeutic inter-

ventions for oral mucositis.

(1) Pain Control [33]. The pain associated with mucositissignificantly affects nutritional intake, oral care, and qualityof life of child. The use of saline mouth rinses, ice chips,and topical mouth rinses containing an anesthetic such as 2%viscous lidocaine relieve pain.

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Table 3: Oral assessment guide [12].

Category Numerical and descriptive ratings1 2 3

Voice Normal Deeper or raspy Difficulty in talking, painfulSwallow Normal swallow Some pain on swallow Unable to swallowLips Smooth, pink, and moist Dry or cracked Ulcerated or bleeding

Tongue Pink and moist and papillae arepresent

Coated or loss of papillae with shinyappearance, with or without redness Blistered/cracked

Saliva Watery Thick or copy Absent

Mucous membrane Pain and moist Reddened or coated (increasedwhiteness) without ulcerations Ulceration with or without bleeding

Gingiva Pink, stippled, and firm Edematous with or without redness Spontaneous bleeding or bleeding onpressure

Teeth or dentures Clean and no debris Plaque or debris in localized areas(between two teeth, if present)

Plaque or debris generalized alonggum line or denture bearing areas

Table 4: WHO analgesic ladder for the 3 stepwise treatments torelieve pain in mucositis [13].

Step 1 Nonopioid∗± adjuvant† Pain persisting orincreasing. Step up

Step 2Opioid for mild tomoderate. Pain ±

nonopioid ± adjuvant

Pain persisting orincreasing. Step up

Step 3Opioid for moderate to

severe pain§± nonopioid ±

adjuvant∗Aspirin, acetaminophen, and nonsteroidal anti-inflammatory drugs.†Amitriptyline, carbamazepine, and gabapentin for neuropathic pain; pred-nisone or dexamethasone for pain associated with intracranial pressure,nerve, and spinal cord compression.‡Codeine, hydrocodone, and tramadol.§Morphine, fentanyl, and hydromorphone.

The stepwise approach that should be followed is asfollows:

(1) beginning with oral rinses (saline solution, sodiumbicarbonate rinses, etc.),

(2) topical anesthetics (lidocaine and benzocaine),(3) mouthwashes combination (“magic mouth rinse”

containing diphenhydramine, lidocaine, and combi-nations of aluminum hydroxide; magnesium hydrox-ide; and simethicone),

(4) mucosal surface protectants such as hydroxypropylcellulose gels or sucralfate solutions.

When these medications do not provide adequate relief,a step-up approach to systemic analgesics is warranted; seeTable 4.

(2) Nutritional Support [33]. Nutritional intake can beseverely compromised by the pain associated with severeoral mucositis and taste changes occur due to chemotherapyand/or radiation therapy that limits food intake [39]. In

patients expected to develop severe mucositis, a gastrostomytube is sometimes placed prophylactically. Guidelines pub-lished by the American Society for Parenteral and EnteralNutrition state that parenteral nutrition should be consideredin children who cannot maintain adequate nutritional intakeorally or enterally for 5 to 7 days. But the potential risks ofparenteral nutrition, including increased risks of infection,electrolyte abnormalities, and cholestatic liver disease, mustbe considered [42].

(3) Oral Decontamination [39]. The microbial colonizationof oral mucositis lesions exacerbates the severity of oralmucositis and decontamination of oral cavity will reduce theseverity of mucositis [10, 39]. Patients who have developedsevere oral mucositis also have been found to be three timesmore likely to develop bacteremias resulting in increasedlength of hospital stays as compared to patients withoutmucositis.

Chlorhexidine [39]. Chlorhexidine mouthwash is effectiveantimicrobial compound and topical prophylactic agentagainst oral mucositis and candidiasis. It acts as a localanesthetic and anti-inflammatory agent that possesses noantimicrobial activity. Cheng and Chang conducted a ran-domized 2-period crossover study that compared the efficacyof 0.15% benzydamine and 0.2% chlorhexidine mouthwashesin alleviating the symptoms of oral mucositis in childrenundergoing chemotherapy. Of the 34 patients who wereevaluated, 26% of the chlorhexidine group compared to 48%of the benzydamine group showed WHO grade II mucositis.The results revealed a significant difference in mouth painand decreased difficulty in eating/chewing and swallowing infavor of chlorhexidine [43].

(4) Palliation of Dry Mouth [33]. Patients undergoing cancertherapy often develop transient or permanent xerostomiaand hyposalivation, which further aggravate inflamed tissues,increase risk for local infection, and make mastication diffi-cult.

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The following measures can be taken for palliation of adry mouth:

(1) sipping water as needed to alleviate mouth dryness.Several supportive products including artificial salivaare available;

(2) rinsing with a solution of 1/2 teaspoon of baking soda(and/or 1/4 or 1/2 teaspoon of table salt) in 1 cupwarmwater several times a day to clean and lubricate theoral tissues and to buffer the oral environment;

(3) chewing sugarless gum to stimulate salivary flow;(4) using cholinergic agents as necessary.

(5) Management of Bleeding [33]. Local intraoral bleeding canusually be controlledwith the use of topical hemostatic agentssuch as fibrin glue or gelatin sponge.

3.2.6. AdvancedTherapeutic Interventions for the Treatment ofOral Mucositis in Children

(1) Cryotherapy [33]. Topical administration of ice chips tothe oral cavity during administration of chemotherapy resultsin decreased delivery of the chemotherapeutic agent to theoral mucosa. This effect is due vasoconstriction and reducedblood flow. Studies conducted by Aisa et al., and Mahood etal. have stated that cryotherapy reduces the severity of oralmucositis in patients receiving bolus doses of chemothera-peutic agents [44, 45].The disadvantage of cryotherapy is thatit is only useful for short bolus chemotherapeutic infusionsand do not have a role in radiation-induced oral mucositis.

(2) Growth Factors [33]. Reduction in the proliferative capac-ity of oral epithelial cells is thought to play a role in thepathogenesis of mucositis, so various growth factors that canincrease epithelial cell proliferation have been studied for themanagement of oral mucositis. A study conducted by VonBultzingslowen et al. showed that IV recombinant humankeratinocyte growth factor-1 significantly reduced incidenceof oral mucositis in patients with hematologic malignanciesreceiving high-dose chemotherapy and total body irradiationbefore autologous hematopoietic cell transplantation [46].Intravenous human fibroblast growth factor-20 is currentlyin clinical development for reduction of mucositis secondaryto high-dose chemotherapy in autologous hematopoietic celltransplant patients [47].

Anti-Inflammatory Agents [33]. Benzydamine hydrochlo-ride is a nonsteroidal anti-inflammatory drug that inhibitsproinflammatory cytokine TNF-𝛼. In one phase III clinicaltrial, benzydamine hydrochloride mouth rinse reduced theseverity of mucositis in patients with head and neck cancerundergoing radiation therapy of cumulative doses up to 50Gyradiation therapies [48].

(3) Antioxidants. A topical oral applicant, RK-0202, consistsof the antioxidant N-acetylcysteine. In a placebo-controlledphase II trial in patients with head and neck cancer, this agent

significantly reduced the incidence of severe oralmucositis upto doses of 50Gy radiation therapies [49].

(4) Glutamine [39]. During times of stress, including cancer,glutamine stores decrease in body by over 50%, contributingto the development of oral mucositis [50].

Use of supplemental glutamine has been said to regulategastrointestinal cell growth, function, and regeneration. Astudy done by Skubitz and Anderson found that glutaminedecreased the duration of mucositis to 4.5 days comparedwith placebo. Glutamine lessened the pain associated withmucositis, specifically pain that altered eating habits [51].Glutamine has no taste and is suspended in a sucrose vehicle,so it will be palatable to children.

Oral Sucralfate Suspension [39]. Sucralfate is used for gastriculcer prophylaxis and treatment. Its mechanism of action isnot clear, but it is believed that sucralfate binds to ulcerations,creating a protective barrier to aid in healing [52]. Shenep andcolleagues conducted a study in 48 children and adolescentswith newly diagnosed acute nonlymphocytic leukemia. Thetreatment group who used sucralfate suspension had showed58% bacterial colonization rate compared to 92% in controlgroup. No oral pain was reported in 58% of patients receivingsucralfate, compared to 25% receiving placebo [53].

(5) Palifermin [39]. As a recombinant keratinocyte growthfactor, palifermin stimulates the proliferation, differentiation,andmigration of epithelial cells throughout the gastrointesti-nal tract. A study was conducted by Vadhan-Raj et al. Eighty-eight percent of the patients receiving placebo experiencedgrade II or higher mucositis, compared to only 44% of thepalifermin treated patients. Opioid use was also decreased inthe palifermin treated group [54].

(6) Low-Level Laser Therapy [33]. The mechanism by whichLLLT accelerates wound healing in mucositis is due to thefollowing [55]:

(1) increased mitochondrial ATP production,(2) the local release of growth factors,(3) increased proliferation of fibroblasts,(4) detoxifying oxygen free radicals or reducing the

formation of these free radicals,(5) increases microcirculation in mucosa.

In a study conducted by Djavid in 45 patients whounderwent chemotherapy, low-level laser therapy signifi-cantly reduced the incidence and duration of grades 3 and 4oral mucositis, decreased the risk of secondary infection, andaccelerated return to normal nutrition [55].

A meta-analysis done by Clarkson et al., (2004), in aCochrane review of 27 publications, found that, among 8prophylactic agents used to obtain relief from mucositis,crushed ice yielded the best results [56]. Keefe et al. (2007)published an update on the clinical guides for the preventionand treatment of oral and gastrointestinal mucositis which iscurrently themost widely used treatment that is the use of 2%

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Table 5: Staging classification and treatment of osteonecrosis of the jaws [14].

Staging classification Clinical manifestations Treatment

Stage 1Exposed bone necrosis or small oral ulcerationwithout exposed bone necrosis, but withoutsymptoms.

Rinses with 0.12% chlorhexidine and checkup.

Stage 2 AExposed bone necrosis or a small oral fistulawithout exposed bone necrosis, but withsymptoms controlled with medical treatment.

Rinses with 0.12% chlorhexidine, antibiotic,analgesics, and checkup.

Stage 2 BExposed bone necrosis or a small oral fistulawithout exposed bone necrosis, but withsymptoms not controlled with medical treatment.

Rinses with 0.12% chlorhexidine, antibiotic,analgesics, and surgery with removal of thezone of bone necrosis.

Stage 3 Jaw fractures, skin fistula, and osteolysisextending to the inferior border.

Rinses with 0.12% chlorhexidine, antibiotic,analgesics, and extensive surgery with resectionof bone.

lidocaine rinses in combination with 0.12–0.2% chlorhexi-dine during 30 seconds, every three or four hours [57]. Colellaet al., (2010) have suggested that the frequent application of aspray consisting of synthetic collagen precursor amino acidsin combination with sodium hyaluronate can offer rapid andeffective pain relief and contributes to mucosal healing [58].

(7) Xerostomia [33]. High-dose irradiation to the head andneck region has been shown to cause changes in the chemicalcomposition of the saliva as well as a reduction in the rate andvolume of salivary flow in adults [59, 60]. Radiation-inducedxerostomia will also cause a shift in the oral microflora to ahighly acidogenic and cariogenic population [61].

A study conducted by Nasman et al. proved that a signif-icantly greater proportion of children treated with total bodyirradiation or chemotherapy harbor high bacterial counts ofStreptococcusmutans in comparisonwith the control childrenand children in the treatment group exhibited a low salivabuffer capacity [62]. Regardless of caries risk, brushing shouldbe done twice daily with fluoridated toothpaste [63].

In addition, daily rinsing with chlorhexidine digluconateis also recommended for children with a high caries risk.Daily use of a self-applied fluoride gel is effective in patientswith xerostomia to prevent dental caries. A regular periodicdental radiographic imaging is needed to monitor caries risk[51].

(8) Trismus [33]. Daily oral stretching exercises/physicaltherapy must continue during radiation treatment. Man-agement of trismus may include prosthetic aids to reducethe severity of fibrosis, trigger-point injections, analgesics,muscle relaxants, and other pain management strategies.

(9) Osteoradionecrosis [14]. The management of osteora-dionecrosis should aim to afford pain relief, control soft tissueand bone infection, and avoid or reduce the progression ofbone necrosis; see Table 5.

The diagnostic criteria of osteoradionecrosis are as fol-lows:

(1) presence of one or more ulcerated mucosal lesion ofthe alveolar processes, with or without the exposureof maxillary or mandibular bone,

(2) exposed bone presenting a necrotic appearance,(3) lesions presenting spontaneously or after dentoalveo-

lar surgery (particularly extractions),(4) absence of healing over a period of at least 6 weeks.

3.3. Phase 3: Dental and Oral Care after the CancerTherapy IsCompleted [16]. The objectives of a dental/oral examinationafter cancer therapy ends are stated below:

(1) to maintain optimal oral health,(2) to reinforce the importance ofoptimal oral and dental

care for life to the patient/parents.

The patient should be seen at least every 6 months or inshorter intervals if issues such as xerostomia or trismus arepresent.

Patients who have experienced moderate or severemucositis are closely monitored for any changes in oralmucosa. Orthodontic care may start or resume after com-pletion of all therapy and after at least a 2-year disease-freesurvival when the risk of relapse is decreased and the patientis no longer using immunosuppressive drugs [64].

Long-Term Effects of Oncotherapy on Pediatric Patients [65].The treatment of leukemia severely alters odontogenesisprocess and the severity depends on the age of the child.The younger the child is, the greater the oral complicationsnoticed as both dentitions, deciduous and permanent, areaffected during the earlier stages of development. The mostcommon changes are microdontia, agenesis of teeth, changein crown or root shape, defective mineralization of the dentalstructure, and delayed tooth eruption [66–68]. Along withchange in tooth size and shape, irradiation also affects growthcenters affectingmaturation of craniofacial complex resultingin asymmetrical facial growth and malocclusion [69].

The degree and severity of these defects depend onthe child’s age at diagnosis, type of central nervous systemtreatment, and the dose of cranial irradiation. Childrentreated before 5 years of age had the most severe dentaldefects, suggesting that immature teeth were at greater riskfor developmental disturbances than mature teeth. Many

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Table 6: Flow chart showing oral and dental care before, during, and after chemotherapy for leukemic children [14].

Treatment before chemotherapy Treatment during chemotherapy Treatment after chemotherapyThe dentist should consult the oncologist todetermine the current condition of the patientand the type of treatment planned.

The oncologist should be consulted inorder to know the degree of immunesuppression of the patient.

The dentist should consult the oncologistto determine immune competence.

(i) Exhaustive examination of the oral cavity:discard periapical lesions and/or bonealterations and the evaluation of periodontalhealth.(ii) Denture fitting should be checked, withreadjustment or removal of those prosthesesthat prove trauma.(iii) Radiological study: intraoral (periapicaland bitewing) and panoramic.

Treatment of the complications ofchemotherapy (mucositis, xerostomia).

(i) Insist on the need for routinesystematic oral hygiene.(ii) Use of chlorhexidine rinses andfluorization.

General prophylactic measures: tartar removal,dental fluorization, and rinses with 0.12%chlorhexidine.

Continued patient reminder of the needto maintain strict dental hygiene isindicated, with the added use ofchlorhexidine rinses and fluorization.

The patient should be informed of thecomplications of treatment.

(i) Analgesics: paracetamol/metamizol.(ii) No NSAID.(iii) Antibiotics: dose adjustment isrequired according to the observedcreatinine clearance values in patientswith kidney problems.

Teeth that are nonviable or present a poorprognosis should be removed:(1) minor surgery: at least two weeks beforechemotherapy.(2) major surgery: 4–6 weeks beforechemotherapy.

No elective dental treatment should becarried out.Only emergency dental care.

Elective dental treatment.

case reports and animal studies confirm this hypothesis andsuggest that dental defects may be related to chemotherapy,radiotherapy, or both [65]. Study conducted by Sonis et al.in 97 children to evaluate craniofacial development in long-term survivors of acute lymphoblastic leukemia found thatcraniofacial effects of therapy were observed in only thosechildren who received 2400 cGy before 5 years of age. Ninetypercent of children in this group had diminished mandibulargrowth that was determined by cephalometric analysis [70].

Another similar study conducted by Guyuron et al., hasshown that among 41 patients who received irradiation tothe head and face during growth thirty-eight of them hadsoft tissue or bony deformities [71]. A postulated mecha-nism, which explains the development of altered craniofacialgrowth in children who underwent craniofacial radiotherapy,is due to that alteration in pituitary gland function [72–74].Recent study done byMinicucci et al. (2003) showed delays indental development, hypoplasia, andmicrodontia in childrenreceiving chemotherapy.

4. Conclusion

The key to success in maintaining a healthy oral cavityduring cancer therapy is patient compliance. It is verymuch vital to educate the caretaker and child about theimportance of oral care to minimize discomfort and increase

the chances for a successful outcome of oncology treatment.Discussionwith caretakers and patient should include dietaryhabits, the potential cariogenicity of pediatric medicationsand nutritional supplements, and late effects of the con-ditioning regimen on the craniofacial growth and dentaldevelopment. The participation of a pediatric dentist in thehematology/oncology team during treatment is of irrefutableimportance in reducing the complications before, during, andafter leukemic treatment in children.

Conflict of Interests

The authors of this paper do not have any conflict of interestseither financially or in any other issues pertaining to thispaper.

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